Tosylates hydroxy group activation

Preparative Methods (1) is easily made by cy clization of commercially available A-Cbz-r-serine (4) under modified Mit-sunobu conditions, using a preformed complex of dimethyl azodicarboxylate (DMAD) and Triphenylphosphine (eq 1). The reaction proceeds via hydroxy group activation, and labeling studies show that the 3-hydroxy group is lost in a 4-exo-tet cyclization mechanism. The p-lactone must be separated quickly from the reaction mixture, and a slight excess of DMAD improves the yield because unreacted triphenylphosphine can cause polymerization. The Boc (f-butoxycarbonyl) analog (2) is prepared similarly, and the p-toluenesulfonate (tosylate) salt (3) is synthesized from (2) by acidic cleavage. ... 

The earliest method developed for the preparation of nonracemic aziridine-2-car-boxylates was the cyclization of naturally occurring (3-hydroxy-a-amino acid derivatives (serine or threonine) [4]. The (3-hydroxy group is normally activated as a tosyl or mesyl group, which is ideal for an intramolecular SN2 displacement. The cyclization has been developed in both one-pot and stepwise fashion [4—9]. As an example, serine ester 3 (Scheme 3.2) was treated with tosyl chloride in the presence of triethylamine to afford aziridine-2-carboxylate 4 in 71% yield [9]. Cyclization of a-hydroxy- 3-amino esters to aziridine-2-carboxylates under similar conditions has also been described [10]. 

Various p-amino thiols are synthesized from the corresponding P-amino alcohols 1 by activation of the hydroxy group to form a tosylate intermediate 2 and then conversion into a thioester 3 5 or direct thioacetylation of the hydroxy group of 1 using the Mitsunobu reaction with diisopropyl azodicarboxylate, triphenylphosphine, and thiolacetic acid as reagents (Scheme l). 6,7 The thioesters 3 are then hydrolyzed and the corresponding disulfide derivatives 4 are produced by iodine oxidation. 7 ... 

Arenesulfonyl derivatives are frequently employed in organic synthesis to activate hydroxy groups for nucleophilic substitution reactions or to protect primary and secondary amines. The PET cleavage of tosyl groups is closely related to reductions... 

Epimerhation of hydroxyl groups. Epimerization of hydroxyl groups is often effected by S 2 displacement of the tosylates of the alcohol with tetraethylammonium acetate (1, 1136-11.37 2. 397) or with tetra-n-butylammonium acetate (3, 277). In connection with a study of configuration and biological activity in the prostaglandins, Corey and Terashima examined the reaction of the tosylatc of the model (-t)-hydroxy-laclone (1) with 5.0 eq. of tetra-n-butylammonium acetate in acetone at 25" for 2 hr. 

New types of acyclic nucleoside phosphonates (408-412) have been obtained using a multistep synthetic approach based on N-1, O- and S-alkylations of 4-and 2,4-substituted 6-hydroxy and 6-mercaptopyrimidines with diisopropyl 2-(chloroethoxy)methylphosphonate and (R) or (S) - [2-(diisopropylphos-phonyl)methoxy] propyl tosylate. Inhibitory activity against viruses of both the nucleoside phosphonates and the related phosphonic acids was investigated. It was found that the 6[2-(phosphonomethoxy)ethoxy]pyrimidines must bear an (unsubstituted) amino group concomitantly on both C-2 and C-4, or an amino on C-2 and an OH group on C-4, to display antiviral activity. Alkyl ethers are preferred over alkyl thioethers. The compounds of the 6-[2-(phos-phonomethoxy)ethoxy] and 6-[2-(phosphonomethoxy) propoxy]pyrimidine... 

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